Several concerns have been raised regarding transgenic crop plants. Foremost is the possibility that the process of genetic engineering might inadvertently generate new allergens or toxins that could affect human health. Another concern is that introduced genes from engineered crops could move to other organisms in the environment. Other concerns relate to cultivars that are engineered to produce insecticides. The potential development of insecticide resistance in target pests is worrisome; as is the possibility that non-target, beneficial insects might be affected by engineered plants.

A particular concern is the possibility that transgenic crop plants could affect human health by expressing unanticipated allergens. In March 1996 researchers at the University of Nebraska showed that an allergen from Brazil nuts had been transferred into soybeans. Individuals sensitized to Brazil nuts make antibodies (IgE) specific to certain proteins in the nuts. Engineered soybeans reacted with such antibodies in vitro. Had allergic individuals consumed the transgenic soybeans they would have likely experienced IgE-mediated reactions, ranging from itching to anaphylaxis.

Obviously, expressing a known allergen in food crops is unwise. However, it is difficult to predict whether a protein expressed in a novel organism will cause allergies. A protein isolated from its native species may differ from the same protein (with an identical amino acid sequence) harvested from a transgenic organism expressing that protein. Sometimes sugar or acetyl groups are added to proteins after they are manufactured at the ribosome. The forms of sugar or acetyl groups may vary between organisms. Sugar groups on proteins have been associated with allergenic and immunogenic responses. Hence, allergenicity studies ought to be carried out on the actual material derived from transgenic plants themselves, rather than on just the bacterial proteins. Such studies are not always done.

Critics are worried that engineered plants might generate toxins as a result of the DNA-insertion process. They note that the insertion of genetic material (using gene gun technology, for example) is semi-random, and that the amount and location of DNA inserted into the chromosome varies. If an insert disrupts a regulatory region that serves to "turn off" the production of a toxin, the result might be an over-expression of toxin. Another concern is the inclusion of regulatory regions as part of genetic constructs: the regulation of host genes near an insert could be dramatically affected.

Significant concerns relate to the impact that genetically modified plants could make on the environment. In experiments, transgenic crops are known to hybridize with closely related species. The probability that transgenic traits, as well as other accompanying changes in traits, will show up in wild plant relatives is increasing as genetically modified crops are established. Herbicide-tolerant weeds can evolve; glyphosphate- (Roundup TM) resistant rigid ryegrass, for example, has developed only recently. Genetically modified crops must be monitored to reduce unintended degradation of natural ecosystems.

Crops engineered to produce insecticides, such as Bt toxin, bring other concerns. The widespread planting of Bt corn and other crops can result in insects evolving a resistance to Bt toxins. At least ten species of moths, two species of beetles, and four species of flies already have developed resistance to Bt toxins under laboratory exposure. Bt toxins administered as a spray are present only transiently. However, transgenic crops continuously express the insecticidal protein. This ongoing exposure may be more likely to select for resistant insects.

The emergence of a resistant insect population is likely whenever a pesticide is used. One strategy for delaying the emergence of insects resistant to Bt toxin is to plant a "refuge" of conventional crops near Bt-expressing crops. The idea is that these conventional crops will harbor susceptible insects that will mate with resistant insects, diluting out recessive resistance alleles. Of course, if resistance develops as a dominant allele, this strategy will not work.

There are hundreds of known subspecies of Bacillus thuringiensis, and the insecticidal toxin derived from each is poisonous only to certain species of insects. Nevertheless, there are concerns that plants expressing genes for such toxins could affect non-target insect species. Some of these species may be beneficial, such as those that provide pollination or consume pests. Laboratory experiments suggest an increased mortality of Monarch butterflies that ingested Bt corn pollen. How frequently this occurs in the field is unknown, and not all laboratory studies have given similar results. The Environmental Protection Agency (EPA) requires toxicity tests on a standard set of organisms before a pesticide can be registered. As of December 2002 the EPA had not demonstrated toxicity of Bt to nontarget species. Data gathering continues.